Attractin Participates in Schizophrenia by Affecting Testosterone Levels

Area of Science:

• Neuroscience
• Genetics
• Endocrinology

Background:

• Attractin (ATRN) is a glycoprotein involved in homeostasis, neurodevelopment, and immunity.
• The ATRN gene is located on chromosome 20p13, a region linked to schizophrenia.
• The role of ATRN in central nervous system disorders requires further investigation.

Purpose of the Study:

• To investigate the role of ATRN in central nervous system disorders.
• To explore the relationship between ATRN, testosterone levels, and behavioral phenotypes.
• To examine the impact of ATRN on sexual dimorphisms in psychiatric conditions.

Main Methods:

• Created an attractin (ATRN) knockout zebrafish model for behavioral and biochemical analysis.
• Measured testosterone levels and gene expression (cyp51, hsd17b7) in zebrafish.
• Compared testosterone levels in 9,008 psychiatric patients and 247 controls, analyzing ATRN expression and mutations in extreme groups.

Main Results:

• ATRN knockout zebrafish exhibited increased attack behavior and elevated testosterone levels.
• Upregulation of testosterone synthesis genes (cyp51, hsd17b7) was observed in ATRN knockout zebrafish brains.
• Male schizophrenia patients had lower testosterone; female schizophrenia and bipolar disorder patients had higher testosterone than controls.
• Reduced ATRN expression and abnormal testosterone levels were found in subjects with ATRN mutations.

Conclusions:

• The interplay between ATRN and testosterone may contribute to sexual dimorphisms observed in behavioral phenotypes.
• ATRN plays a role in regulating testosterone synthesis and behavior.
• Altered ATRN and testosterone levels are associated with psychiatric disorders.